Cancer aneuploidies are shaped primarily by effects on tumour fitness.

Aneuploidies-whole-chromosome or whole-arm imbalances-are the most prevalent alteration in cancer genomes1,2. However, it is still debated whether their prevalence is due to selection or ease of generation as passenger events1,2. Here we developed a method, BISCUT, that identifies loci subject to fitness advantages or disadvantages by interrogating length distributions of telomere- or centromere-bounded copy-number events. These loci were significantly enriched for known cancer driver genes, including genes not detected through analysis of focal copy-number events, and were often lineage specific. BISCUT identified the helicase-encoding gene WRN as a haploinsufficient tumour-suppressor gene on chromosome 8p, which is supported by several lines of evidence. We also formally quantified the role of selection and mechanical biases in driving aneuploidy, finding that rates of arm-level copy-number alterations are most highly correlated with their effects on cellular fitness1,2. These results provide insight into the driving forces behind aneuploidy and its contribution to tumorigenesis.

Recent Thymic Emigrants Require RBPJ-Dependent Notch Signaling to Transition into Functionally Mature Naive T Cells.

Recent thymic emigrant (RTE) cells are nascent T cells that continue their post-thymic maturation in the periphery and dominate T cell immune responses in early life and in adults having undergone lymphodepletion regimens. However, the events that govern their maturation and their functionality as they transition to mature naive T cells have not been clearly defined. Using RBPJind mice, we were able to identify different stages of RTE maturation and interrogate their immune function using a T cell transfer model of colitis. As CD45RBlo RTE cells mature, they transition through a CD45RBint immature naive T (INT) cell population that is more immunocompetent but shows a bias toward IL-17 production at the expense of IFN-γ. Additionally, the levels of IFN-γ and IL-17 produced in INT cells are highly dependent on whether Notch signals are received during INT cell maturation or during their effector function. IL-17 production by INT cells showed a total requirement for Notch signaling. Loss of Notch signaling at any stage of INT cells resulted in an impaired colitogenic effect of INT cells. RNA sequencing of INT cells that had matured in the absence of Notch signals showed a reduced inflammatory profile compared with Notch-responsive INT cells. Overall, we have elucidated a previously unknown INT cell stage, revealed its intrinsic bias toward IL-17 production, and demonstrated a role for Notch signaling in INT cell peripheral maturation and effector function in the context of a T cell transfer model of colitis.

Tangent normalization for somatic copy-number inference in cancer genome analysis.

MOTIVATION: Somatic copy-number alterations (SCNAs) play an important role in cancer development. Systematic noise in sequencing and array data present a significant challenge to the inference of SCNAs for cancer genome analyses. As part of The Cancer Genome Atlas, the Broad Institute Genome Characterization Center developed the Tangent normalization method to generate copy-number profiles using data from single-nucleotide polymorphism (SNP) arrays and whole-exome sequencing (WES) technologies for over 10 000 pairs of tumors and matched normal samples. Here, we describe the Tangent method, which uses a unique linear combination of normal samples as a reference for each tumor sample, to subtract systematic errors that vary across samples. We also describe a modification of Tangent, called Pseudo-Tangent, which enables denoising through comparisons between tumor profiles when few normal samples are available. RESULTS: Tangent normalization substantially increases signal-to-noise ratios (SNRs) compared to conventional normalization methods in both SNP array and WES analyses. Tangent and Pseudo-Tangent normalizations improve the SNR by reducing noise with minimal effect on signal and exceed the contribution of other steps in the analysis such as choice of segmentation algorithm. Tangent and Pseudo-Tangent are broadly applicable and enable more accurate inference of SCNAs from DNA sequencing and array data. AVAILABILITY AND IMPLEMENTATION: Tangent is available at https://github.com/broadinstitute/tangent and as a Docker image (https://hub.docker.com/r/broadinstitute/tangent). Tangent is also the normalization method for the copy-number pipeline in Genome Analysis Toolkit 4 (GATK4). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Obesity is Associated With Greater Improvement in Patient-Reported Outcomes Following Primary Total Knee Arthroplasty.

BACKGROUND: Body mass index (BMI) cutoffs have been established for total knee arthroplasty (TKA) patients due to increased risk of medical complications in obese patients. However, evidence-based medical optimization may mitigate risk in these patients. This study examined the influence of BMI on patient-reported outcome measures (PROMs) following primary TKA with specialized perioperative optimization. METHODS: Between 2016 and 2020, 1,329 consecutive primary TKAs using standardized perioperative optimization were retrospectively reviewed. Patients were categorized into ordinal groups based on BMI in 5 kg/m2 increments (range, 17 to 61). Primary outcomes related to activity level, pain, function, and satisfaction were evaluated. BMI groups ≥35 had significantly lower age, more women, and higher prevalence of comorbidities (P ≤ .004). Mean follow-up was 1.7 years (range, 1 to 5 years). RESULTS: Each successive BMI group from 35 to ≥50 demonstrated continually greater improvement in pain with level walking and stair climbing (P ≤ .001), Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (P = .001), and greater satisfaction (P = .007). No patients who had a BMI ≥35 were revised for aseptic loosening, and rates of periprosthetic joint infection were not different between BMI groups (P = 1.000). CONCLUSION: Despite being more debilitated preoperatively, patients who had a BMI ≥35 experienced greater improvements in PROMs compared to patients who had lower BMI. Given the significant improvements in PROMs and quality of life in obese patients, with appropriate perioperative optimization, these patients should not be prohibited from having a TKA when appropriately indicated. LEVEL OF EVIDENCE: III.

Assessment and validation of a novel fast fully automated artificial intelligence left ventricular ejection fraction quantification software.

BACKGROUND: Quantification of left ventricular ejection fraction (LVEF) by transthoracic echocardiography (TTE) is operator-dependent, time-consuming, and error-prone. LVivoEF by DIA is a new artificial intelligence (AI) software, which displays the tracking of endocardial borders and rapidly quantifies LVEF. We sought to assess the accuracy of LVivoEF compared to cardiac magnetic resonance imaging (cMRI) as the reference standard and to compare LVivoEF to the standard-of-care physician-measured LVEF (MD-EF) including studies with ultrasound enhancing agents (UEAs). METHODS: In 273 consecutive patients, we compared MD-EF and AI-derived LVEF to cMRI. AI-derived LVEF was obtained from a non-UEA four-chamber view without manual correction. Thirty-one patients were excluded: 25 had interval interventions or incomplete TTE or cMRI studies and six had uninterpretable non-UEA apical views. RESULTS: In the 242 subjects, the correlation between AI and cMRI was r = .890, similar to MD-EF and cMRI with r = .891 (p = 0.48). Of the 126 studies performed with UEAs, the correlation of AI using the unenhanced four-chamber view was r = .89, similar to MD-EF with r = .90. In the 116 unenhanced studies, AI correlation was r = .87, similar to MD-EF with r = .84. From Bland-Altman analysis, LVivoEF underreported the LVEF with a bias of 3.63 ± 7.40% EF points compared to cMRI while MD-EF to cMRI had a bias of .33 ± 7.52% (p = 0.80). CONCLUSIONS: Compared to cMRI, LVivoEF can accurately quantify LVEF from a standard apical four-chamber view without manual correction. Thus, LVivoEF has the ability to improve and expedite LVEF quantification.

Identification of Widespread Antibiotic Exposure in Patients With Cholera Correlates With Clinically Relevant Microbiota Changes.

BACKGROUND: A first step to combating antimicrobial resistance in enteric pathogens is to establish an objective assessment of antibiotic exposure. Our goal was to develop and evaluate a liquid chromatography-ion trap mass spectrometry (LC/MS) method to determine antibiotic exposure in patients with cholera. METHODS: A priority list for targeted LC/MS was generated from medication-vendor surveys in Bangladesh. A study of patients with and those without cholera was conducted to collect and analyze paired urine and stool samples. RESULTS: Among 845 patients, 11% (90) were Vibrio cholerae positive; among these 90 patients, analysis of stool specimens revealed ≥1 antibiotic in 86% and ≥2 antibiotics in 52%. Among 44 patients with cholera and paired urine and stool specimens, ≥1 antibiotic was detected in 98% and ≥2 antibiotics were detected in 84%, despite 55% self-reporting medication use. Compared with LC/MS, a low-cost antimicrobial detection bioassay lacked a sufficient negative predictive value (10%; 95% confidence interval, 6%-16%). Detection of guideline-recommended antibiotics in stool specimens did (for azithromycin; P = .040) and did not (for ciprofloxacin) correlate with V. cholerae suppression. A nonrecommended antibiotic (metronidazole) was associated with decreases in anaerobes (ie, Prevotella organisms; P < .001). CONCLUSION: These findings suggest that there may be no true negative control group when attempting to account for antibiotic exposure in settings like those in this study.

Narcissism and the pursuit of status.

OBJECTIVE: The purpose of the present studies was to examine the connections that narcissistic admiration and narcissistic rivalry had with various aspects of status. METHOD: Study 1 examined the associations that narcissism had with the motivation to seek status in a sample of 1,219 community members. Study 2 examined whether narcissism interacted with the status-seeking motive to predict how individuals pursued status in a sample of 760 community members and college students. Study 3 used a daily diary approach to examine whether narcissism moderated the associations that daily perceptions of status and affiliation had with state self-esteem in 356 college students. RESULTS: Our results revealed that narcissistic admiration and narcissistic rivalry were somewhat similar in their desire for status but had divergent associations with other aspects of status (e.g., strategies employed to attain status, perceptions of status, reactions to perceived status). CONCLUSIONS: The results of the present studies suggest that narcissistic admiration is associated with an agentic orientation to the pursuit of status, whereas narcissistic rivalry is associated with an antagonistic orientation to the pursuit of status. Discussion focuses on the implications of these results for our understanding of the connections between narcissism and status.

G-Quadruplex Supramolecular Assemblies in Photochemical Upconversion.

Parallel, tetramolecular G-quadruplex (G4) DNA possessing TINA monomer, (R)-1-O-[4-(1-pyrenylethynyl)phenylmethyl]glycerol, were synthesised and evaluated in complexes with tris(2,2'-bipyridine)ruthenium(II), [Ru(bpy)3 ](2+) , and the Zn(2+) derivative of 5,10,15,20-tetrakis-(1-methyl-4-pyridyl)-21 H,23H-porphine, ZnTMpyP4. UV/Vis, fluorescence, and circular dichroism (CD) spectroscopy showed that the use of G4-DNA as a template resulted in the effective communication between the ligands and the TINA molecule that was covalently attached to the 5'-end and between T and dG at the 5'-end of the dTG4 T sequence. Only one G4-DNA possessing the TINA molecule at the 5'-end of the dTG4 T sequence was able to yield a green-to-blue photochemical upconversion (PUC, λem =420 nm) in the presence of [Ru(bpy)3 ](2+) upon excitation at 500 nm. Different DNA secondary structures can thus be used in DNA-based assemblies for PUC and the way of attachment of chromophores to DNA plays a pivotal role for the creation of a photosynthetic centre.

Knowledge co-production and boundary work to promote implementation of conservation plans.

Knowledge co-production and boundary work offer planners a new frame for critically designing a social process that fosters collaborative implementation of resulting plans. Knowledge co-production involves stakeholders from diverse knowledge systems working iteratively toward common vision and action. Boundary work is a means of creating permeable knowledge boundaries that satisfy the needs of multiple social groups while guarding the functional integrity of contributing knowledge systems. Resulting products are boundary objects of mutual interest that maintain coherence across all knowledge boundaries. We examined how knowledge co-production and boundary work can bridge the gap between planning and implementation and promote cross-sectoral cooperation. We applied these concepts to well-established stages in regional conservation planning within a national scale conservation planning project aimed at identifying areas for conserving rivers and wetlands of South Africa and developing an institutional environment for promoting their conservation. Knowledge co-production occurred iteratively over 4 years in interactive stake-holder workshops that included co-development of national freshwater conservation goals and spatial data on freshwater biodiversity and local conservation feasibility; translation of goals into quantitative inputs that were used in Marxan to select draft priority conservation areas; review of draft priority areas; and packaging of resulting map products into an atlas and implementation manual to promote application of the priority area maps in 37 different decision-making contexts. Knowledge co-production stimulated dialogue and negotiation and built capacity for multi-scale implementation beyond the project. The resulting maps and information integrated diverse knowledge types of over 450 stakeholders and represented >1000 years of collective experience. The maps provided a consistent national source of information on priority conservation areas for rivers and wetlands and have been applied in 25 of the 37 use contexts since their launch just over 3 years ago. When framed as a knowledge co-production process supported by boundary work, regional conservation plans can be developed into valuable boundary objects that offer a tangible tool for multi-agency cooperation around conservation. Our work provides practical guidance for promoting uptake of conservation science and contributes to an evidence base on how conservation efforts can be improved.

Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL.

Proteolysis Targeting Chimera (PROTAC) technology is a rapidly emerging alternative therapeutic strategy with the potential to address many of the challenges currently faced in modern drug development programs. PROTAC technology employs small molecules that recruit target proteins for ubiquitination and removal by the proteasome. The synthesis of PROTAC compounds that mediate the degradation of c-ABL and BCR-ABL by recruiting either Cereblon or Von Hippel Lindau E3 ligases is reported. During the course of their development, we discovered that the capacity of a PROTAC to induce degradation involves more than just target binding: the identity of the inhibitor warhead and the recruited E3 ligase largely determine the degradation profiles of the compounds; thus, as a starting point for PROTAC development, both the target ligand and the recruited E3 ligase should be varied to rapidly generate a PROTAC with the desired degradation profile.

Refractive Predictability of Two Intraocular Lens Power Formulas in Long, Medium, and Short Eyes Using a Swept Source Optical Coherence Tomography Biometer.

Purpose: To compare the refractive predictability of Argos measurements with Barrett Universal II (BUII) and Barrett True Axial Length (BTAL) formulas in a large sample of long, medium, and short axial length (AL) eyes. Methods: A retrospective chart review identified 445 eyes of 247 patients for inclusion. The Argos was used for preoperative biometry, and BUII formula for intraocular lens (IOL) power calculations. Back calculations were performed using data from the Argos for the BTAL formula. Data were collected for postoperative absolute prediction error (APE), refractive outcomes, and monocular uncorrected and distance corrected visual acuities at distance (UDVA, CDVA). Results: Overall, mean APE was 0.36 ± 0.33 D for BUII and for 0.34 ± 0.32 D BTAL (p = 0.04). In short AL eyes, mean APE was 0.45 ± 0.37 D for BUII and for 0.37 ± 0.31 D BTAL (p < 0.001). No significant differences between BUII and BTAL were identified for long AL or medium AL eyes. The percentages of eyes with APE of 0.5 D or less in long, medium, and short eyes were 79%, 79% and 51%, respectively, for BUII and 82%, 78% and 69%, respectively, for BTAL. Conclusion: The prediction accuracies were high with both the BUII and BTAL formulas in long, medium, and short eyes, leading to excellent refractive outcomes. The BTAL formula may have lower absolute prediction error in short eyes compared to BUII.

When the natural lens inside the eye becomes opaque, it can be replaced during cataract surgery with a clear artificial intraocular lens (IOL). It is critical for good postoperative outcomes that the optimal power for the IOL is implanted. Biometers are devices used to measure the eye and typically have built-in formulas to calculate the most appropriate IOL power for implantation. However, it is challenging to select the optimal power in eyes that are longer or shorter than average. The purpose of this study was to compare the refractive predictability of a novel biometer using two IOL power calculation formulas in a large sample of long, medium, and short eyes. The results of this study suggest that predictability was high with both formulas in long, medium, and short eyes, leading to excellent refractive outcomes.

Nurses' attitudes, behaviours, and enablers of intravenous to oral switching (IVOS) of antibiotics: a mixed-methods survey of nursing staff in secondary care hospitals across the Midlands region of England.

BACKGROUND: Intravenous (IV) antibiotic use in secondary care in England is widespread. Timely appropriate intravenous to oral switch (IVOS) has the potential to deliver significant clinical and operational benefits. To date, antimicrobial stewardship (AMS) efforts around IVOS have not focused on the nursing staff who administer antibiotics, which represents a significant gap in AMS programmes. AIM: To determine the involvement of bedside nurses in acute trusts in the Midlands region of England in IVOS in their organizations and describe their views regarding how to improve IVOS. METHODS: An anonymous self-administered mixed-methods online survey was developed and distributed to nursing staff in acute trusts via antimicrobial stewardship networks between March and May 2023. Quantitative data was analysed to describe participant demographics and behaviours, whereas barriers and enablers to IVOS were explored through thematic content analysis of responses to open-ended questions. FINDINGS: A total of 545 nursing staff responded to the survey. The majority (65.3%) routinely suggested IVOS to clinicians, despite only 50.6% being aware of local IVOS policies. One-third (34.7%) did not suggest IVOS, relying on doctors, believing their patients needed IV treatment, or lacked knowledge and skills to request IVOS. Content analysis of suggestions for improving the rate of IVOS proposed three major themes (People, Process, System) and identified that education and training, improved confidence and interprofessional relationships, and prompts were important drivers. CONCLUSION: Nursing staff suggest IVOS to other clinicians, but more education and resources are needed to enable and empower them in this role.

Effects of Cholecystokinin on Esophageal Motor Response to Distension in Asymptomatic Volunteers.

Background/Aims: Cholecystokinin (CCK) administration has been shown to reduce lower esophageal sphincter (LES) pressure in normal subjects in manometric studies. Functional luminal imaging probe (FLIP) panometry offers a method to assess esophageal motility in response to sustained distension though mechanisms related to this response remain unexplored. The aim of this study is to evaluate the effect of CCK-8 on the esophageal response to distension in asymptomatic volunteers using FLIP. Methods: Esophageal response to distension was studied in 7 asymptomatic volunteers (mean age ± SD [27 ± 2]; 86% female) before and after CCK-8 administration in a crossover study design. During sedated endoscopy, FLIP was performed twice with CCK-8 administered via intravenous push in one of 2 protocols: during filling (n = 4) or during emptying (n = 3). Esophagogastric junction distensibility index (EGJ-DI) at 60 mL fill volume and esophageal body contractile response patterns were analyzed. Results: During the baseline FLIP study, all subjects had a contractile response with repetitive antegrade contractions both before and after CCK-8 administration. However, a sustained LES contraction or a sustained occluding contraction with esophageal shortening was observed in all subjects in the filling protocol, but in none during the emptying protocol. EGJ-DI was similar before and after CCK-8 during both filling (4.7 ± 1.9 mm2/mmHg vs 4.3 ± 1.8 mm2/mmHg) and emptying protocol (7.5 ± 1.4 mm2/mmHg vs 6.9 ± 0.6 mm2/mmHg). Conclusion: While EGJ-DI appeared unaffected by CCK-8 administration in asymptomatic volunteers, CCK induced spastic-reactive contractions of the LES during distention suggesting that exogenous CCK interferes with normal LES relaxation during secondary peristalsis.

Prognostic and therapeutic implications of tumor-restrictive type III collagen in the breast cancer microenvironment.

Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of in vitro, in vivo and bioinformatic experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer. We demonstrate that Col3-deficient, human fibroblasts produce tumor-permissive collagen matrices that drive cell proliferation and suppress apoptosis in non-invasive and invasive breast cancer cell lines. In human triple-negative breast cancer biopsy samples, we demonstrate elevated deposition of Col3 relative to type I collagen (Col1) in non-invasive compared to invasive regions. Similarly, bioinformatics analysis of over 1000 breast cancer patient biopsies from The Cancer Genome Atlas BRCA cohort revealed that patients with higher Col3:Col1 bulk tumor expression had improved overall, disease-free, and progression-free survival relative to those with higher Col1:Col3 expression. Using an established 3D culture model, we show that Col3 increases spheroid formation and induces the formation of lumen-like structures that resemble non-neoplastic mammary acini. Finally, our in vivo study shows co-injection of murine breast cancer cells (4T1) with rhCol3-supplemented hydrogels limits tumor growth and decreases pulmonary metastatic burden compared to controls. Taken together, these data collectively support a tumor-suppressive role for Col3 in human breast cancer and suggest that strategies that increase Col3 may provide a safe and effective therapeutic modality to limit recurrence in breast cancer patients.

The view from the looking glass: how are narcissistic individuals perceived by others?

Previous studies have found that narcissistic individuals are often viewed negatively by those who know them well. The present study sought to extend these previous findings by examining whether normal and pathological aspects of narcissism were associated with perceiver ratings of narcissistic characteristics and aggression. This was accomplished by having each of our undergraduate participants (288 targets) recruit friends or family members to complete ratings of the target who recruited them (1,296 perceivers). Results revealed that perceived entitlement was strongly associated with perceived aggression. Further, self-reported levels of pathological narcissism moderated these results such that vulnerable narcissism exacerbated the association between perceived entitlement and aggression, whereas grandiose narcissism mitigated the association. The discussion will focus on the implications of these results for understanding the various features of narcissism.

The status-signaling property of self-esteem: the role of self-reported self-esteem and perceived self-esteem in personality judgments.

OBJECTIVE: The provision of information appears to be an important feature of self-esteem. The present studies examined whether self-esteem possesses a status-signaling property such that an individual's level of self-esteem is associated with how the individual is perceived by others. METHOD: In Study 1, trained judges watched brief videos of 157 participants and rated targets as having higher levels of self-esteem when the targets were believed to possess more positive personality characteristics. Study 2 found that participants (357 targets) were rated as having higher levels of self-esteem when they were given more positive personality evaluations by their friends and family members (1,615 perceivers). RESULTS: Consistent with the proposed status-signaling model, high levels of self-esteem were generally associated with the perception of positive personality characteristics. CONCLUSIONS: These findings are discussed in the context of an extended informational model of self-esteem consisting of both the status-tracking and status-signaling properties of self-esteem.

Neuroticism and negative affect influence the reluctance to engage in destructive obedience in the Milgram paradigm.

The present study employed a variation of Milgram's (1963, 1965, 1974) obedience paradigm that required undergraduate participants (N = 33) to administer noise blasts rather than electric shocks. We found that the individuals who were the most reluctant to obey the commands of the experimenter to continue with the procedure were those with low levels of neuroticism who reported the highest levels of negative affect during the session. This suggests that our procedure may offer a relatively benign means for examining the mechanisms underlying destructive obedience as well as individual differences in the willingness to obey authority.

The Evaluation and Management of Coronary Artery Disease in the Lung Transplant Patient.

Lung transplantation can greatly improve quality of life and extend survival in those with end-stage lung disease. In order to derive the maximal benefit from such a procedure, patients must be carefully selected and be otherwise healthy enough to survive a high-risk surgery and sometimes prolonged immunosuppressive therapy following surgery. Patients therefore must be critically assessed prior to being listed for transplantation with close attention paid towards assessment of cardiovascular health and operative risk. One of the biggest dictators of this is coronary artery disease. In this review article, we discuss the assessment and management of coronary artery disease in the potential lung transplant candidate.

Tumor-restrictive type III collagen in the breast cancer microenvironment: prognostic and therapeutic implications.

Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of in vitro, in vivo and in silico experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer. We demonstrate that Col3-deficient, human fibroblasts produce tumor-permissive collagen matrices that drive cell proliferation and suppress apoptosis in noninvasive and invasive breast cancer cell lines. In human TNBC biopsy samples, we demonstrate elevated deposition of Col3 relative to type I collagen (Col1) in noninvasive compared to invasive regions. Similarly, in silico analyses of over 1000 breast cancer patient biopsies from The Cancer Genome Atlas BRCA cohort revealed that patients with higher Col3:Col1 bulk tumor expression had improved overall, disease-free and progression-free survival relative to those with higher Col1:Col3 expression. Using an established 3D culture model, we show that Col3 increases spheroid formation and induces formation of lumen-like structures that resemble non-neoplastic mammary acini. Finally, our in vivo study shows co-injection of murine breast cancer cells (4T1) with rhCol3-supplemented hydrogels limits tumor growth and decreases pulmonary metastatic burden compared to controls. Taken together, these data collectively support a tumor-suppressive role for Col3 in human breast cancer and suggest that strategies that increase Col3 may provide a safe and effective modality to limit recurrence in breast cancer patients.

A case report of acute heart failure and cardiogenic shock caused by catastrophic antiphospholipid syndrome and lupus myocarditis.

Background: Catastrophic antiphospholipid syndrome and lupus myocarditis are two rare life-threatening conditions. Case summary: We present a case of a 47-year-old woman admitted in profound cardiogenic shock due to catastrophic antiphospholipid syndrome and lupus myocarditis requiring advanced heart failure therapies, including early mechanical circulatory support. She improved with steroids, immunoglobulins, mycophenolate, and eculizumab. Discussion: This case highlights the importance of early identification of cardiogenic shock secondary to catastrophic antiphospholipid syndrome and lupus myocarditis, the arrhythmogenic complications of myocarditis, and the subsequent management of the disease progression with mechanical and medical support.